PXD003486

PXD003486 is an original dataset announced via ProteomeXchange.

Title	Quantitative cross-linking/mass spectrometry analysis revealed unknown structure of complement iC3
Description	We applied quantitative cross-linking/mass spectrometry (QCLMS) to interrogate the structure of iC3 (or C3(H2O)), the activated hydrolytic product of the abundant human complement protein C3. The slow but spontaneous and ubiquitous formation of iC3 from C3 initiates antibody-independent activation of the complement system that is a key first line of antimicrobial defense. QCLMS revealed structural differences and similarities between iC3 and C3, as well as between iC3 and C3b that is a pivotal proteolytic cleavage product of C3 and is functionally similar to iC3. Considered in combination with the crystal structures of C3 and C3b, our data support a model wherein the thioester-containing domain of C3 swings to the other end of the molecule creating, in iC3, a stable C3b-like platform for binding the zymogen, factor B, or the regulator, factor H. The integration of available crystallographic and QCLMS data allowed the determination of a 3D model for iC3. The unique arrangement of domains in iC3, which retains the anaphylatoxin (ANA) domain (while ANA is excised when C3 is enzymatically activated to C3b), is consistent with observed differences in activation and regulation between iC3 and C3b.
HostingRepository	PRIDE
AnnounceDate	2016-06-17
AnnouncementXML	Submission_2016-06-17_02:30:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhuo Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-01-19 01:57:17	ID requested
⏵ 1	2016-06-17 02:30:32	announced

Chen ZA, Pellarin R, Fischer L, Sali A, Nilges M, Barlow PN, Rappsilber J, Structure of Complement C3(H2O) Revealed By Quantitative Cross-Linking/Mass Spectrometry And Modeling. Mol Cell Proteomics, 15(8):2730-43(2016) [pubmed]

curator keyword: Biological

submitter keyword: Quantitative cross-linking/mass spectrometry

domain architecture

activation of complement system

alternative pathway

Juri Rappsilber
contact affiliation	1. Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, UK 2. Department of Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, Germany
contact email	juri.rappsilber@ed.ac.uk
lab head
Zhuo Chen
contact affiliation	University of Edinburgh
contact email	zhuo.chen@ed.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/06/PXD003486

PRIDE project URI

• PRIDE
  1. PXD003486
     1. Label: PRIDE project
     2. Name: Quantitative cross-linking/mass spectrometry analysis revealed unknown structure of complement iC3